DESCRIPTION (Scanned from the Applicant's Abstract): Diabetes affects 16 million Americans, producing severe and fatal health complications. In 1998, diabetes cost the nation nearly $100 Billion. Approximately 25 percent of people with diabetes develop leg and/or foot problems; it has been estimated that half of lower-limb amputations could be prevented by improving foot care. Diabetes complications are essentially vascular. Since adenosine increases endothelial cell proliferation and skin fibroblast growth, the objective is to develop a topical formulation to increase blood flow and prevent and/or heal diabetes skin complications. If such effects occur in rats with streptozotocin-induced diabetes (Phase I), utility against diabetes-induced dermal pathology may be anticipated. A quantitative endpoint for success (increased dermal blood flow measured by laser Doppler) makes these studies practicable. In Phase II, tissues obtained at necropsy are evaluated microscopically and studied to ascertain the intracellular signals involved. The objective of Phase II will be to characterize how the topical formulations improves dermal blood flow in streptozotocin-induced diabetes, and to evaluate safety and efficacy of optimized topical formulations. The long-term goal is to identify and develop topical formulations to prevent and/or treat dermal complications of diabetes. The commercial availability of such topical drugs would represent a tremendous improvement in diabetes care. PROPOSED COMMERCIAL APPLICATION: Prevention and treatment of diabetic ulcers.